The long-term objectives of this proposal are to understand the neurobiological basis of individual differences in socio-communicative behavior and cognition in primates, joint attention. One aim of the proposed studies is to PET image chimpanzees while engaged or not engaged in a joint attention task. From the PET images, we will test whether Broca's and Wernicke's areas are joint attention by comparing standardized PET values in cytoarchitectonically derived regions of interest. Furthermore, a whole brain t-map of significantly active brain regions will be derived from the PET analysis to more fully capture the neural systems involved in joint attention. From this PET analysis, we will create objects or masks of the significantly active clusters and these will then be used as regions-of-interest to quantify grey matter proportions from individually segmented MRI scans in more than 100 chimpanzees. The grey matter proportions will be computed and regressed on performance measures for test of joint attention available in these apes to determine, which if any, grey matter proportions predict individual differences in join attention. A second focus of the proposed studies seeks to determine whether the morphology of supragranular pyramidal neurons differ between hemispheres and cortical areas including the inferior frontal gyrus (BA44, BA45), planum temporale (BA22), precentral gyrus (BA4), Heschl's gyrus (BA41/42), and striate cortex (BA17) in chimpanzees. For these studies, we will Golgi stain post-mortem brain tissue and quantify both neuropil space and dendritic arborization for each region of interest in the left and right hemisphere. In one set of analyses, we will test whether chimpanzees show population-level asymmetries by comparing the left and right hemisphere values for each region. In addition, because we have existing data on joint attention in many of the chimpanzees for which post-mortem data are or will be available, we will assess whether individual differences in joint attention are associated with volumetric or lateralized differences in neuropil space or dendritic arborization. Finally, gene and protein expression levels for molecules that are involved in synapse function and neurotransmission within BA44, BA45, BA22, BA4, BA41/42 and BA17 will also be quantified in the chimpanzee post-mortem tissue. For each region-of-interest, we will use stereologic methods to compute volume, neuron counts, and neuron density. After determining the location of each cortical area based on architectonics, adjacent tissue sections will be selected for use in Western blot and qRT-PCR analyses to examine regional and hemispheric variation in the expression of proteins and genes that are important for neuronal function. Consistent with the overarching theme of this proposal, we will test whether chimpanzees show population-level asymmetries and whether individual differences in joint attention are associated with volumetric or lateralized differences in gene and protein expression levels. PUBLIC HEALTH RELEVANCE: Joint attention is a critical skill and foundation for normal socio-communicative development in children and appears to be disrupted in certain neurodevelopmental disorders, such as autism. The proposed studies aim to investigate the neural correlates of individual differences in joint attention at a micro- and macro-structural level of analysis of the cortex.